The folate receptor (FR) is a glycoprotein that is over-expressed in many types of cancer cells and inflammatory cells, but is minimally distributed in normal tissues. For example, folate receptors are over-expressed in a number of human epithelial cancers, including cancer of the ovary, lung, brain (primary and metastatic), endometrium, and kidney, and inflammatory cells of the immune system, such as macrophages and monocytes. Whereas folic acid enters most normal cells via the reduced folate carrier, it is known that the folate receptor, via receptor mediated endocytosis, is capable of internalizing folate conjugates, thus offering a route to target cancerous cells or inflammatory cells, for example.
Folate-targeted technology may be clinically useful, in that folate-linked imaging agents can be used to identify folate receptor (FR) expression on cancer cells, for example. For cancers, FR expression has traditionally been determined through immunohistochemical (IHC) analysis of archived tissue specimens derived at the time of the primary resection/histologic characterization of the cancer. Since FR expression may change during the course of the disease, IHC analysis may be conducted on tissue that is not temporally related to the current state of FR expression in patients. PET, MRI and SPECT/CT imaging techniques can image tissue in almost real-time without the invasiveness of biopsies, and non-invasive folate-targeted imaging agents are important advancements in the field.